Indium-Catalyzed Friedel–Crafts Alkylation of Monosubstituted Benzenes by 1-Bromoadamantane

Abstract

Indium salts such as InCl₃ and InBr₃ (ca. 1–5 mol%) ­efficiently catalyzed the Friedel–Crafts reaction of 1-bromo­adamantane with benzene and monosubstituted benzenes to give 1-adamantyl benzenes. Indium bromide enabled faster reactions than indium chloride but the latter was more suitable in the case of halobenzenes.

Key words

adamantanes - alkylation - catalysis - indium - Lewis ­acids

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• 20 Using more InBr₃ than 0.05 equiv favored the formation of a small amount of the more polar 1,3-diphenyladamantane.
• 21 Indium mesylate and tosylate were prepared by dissolving metallic indium powder in aqueous methanesulfonic acid (3.2 equiv) or p-toluenesulfonic acid (3.0 equiv) at 70 °C (respectively 0.3 and 0.8 mL H₂O/mmol In was used) for respectively 2 and 20 h, followed by removal of water under vacuum at 70 °C. Remarkably, in contrast to indium mesylate and halides, indium tosylate did not exhibit appreciable hygroscopicity, a fact that made it far more convenient to handle.
• 22 Representative Procedure: InBr₃ (7.1 mg, 0.02 mmol) was introduced in an oven- or flame-dried 10 mL round-bottomed flask followed by an olive-shaped magnetic stirring bar. The apparatus was dried by heating for 1–2 min with a heat gun under vacuum. 1-Bromoadamantane (1; 86 mg, 0.4 mmol) and the monosubstituted benzene 2a–h (or benzene itself, 1 mL) were added. The flask was flushed under nitrogen and well stoppered.²⁶ The reaction was left under gentle stirring in a water or oil bath at the specified temperature (see Tables) with protection against light by aluminum foil. After reaction for the specified time (see Tables), abundant evolution of hydrogen bromide (white smoke, caution!) occurred on opening. The reaction mixture was taken up with pentane and washed with water until neutral. After drying (Na₂SO₄) and concentration, chromatography on silica gel (ca. 3 g), eluting with pentane, afforded monoadamantylated benzene 3a–h followed in some cases by more polar 1-bromo-3-aryladamantane (4) and 1,3-diaryladamantane (5). 1-Phenyladamantane (3a): Mp 82 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.37 (dm, J ~ 8 Hz, 2 H), 7.31 (ddm, J = 8.2, 6.8 Hz, 2 H), 7.17 (ddt, J = 7.6, 6.7, 1.4 Hz, 1 H), 2.12–2.07 (m, 3 H), 1.92 (d, J = 2.8 Hz, 6 H), 1.83–1.72 (m, 6 H). ¹³C NMR (100 MHz, CDCl₃): δ = 151.34 (1C_q), 128.10 (2CH), 125.50 (1CH), 124.84 (2CH), 43.23 (3CH₂), 36.88 (3CH₂), 36.22 (1C_q), 29.04 (3CH). 1-(4-Methylphenyl)adamantane (3b): Mp 97–98 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.26 (half of an A₂X₂ system, 2 H), 7.13 (half of an A₂X₂ system coupled with CH₃, J _{with Me} = 0.7 Hz, 2 H), 2.32 (t, J = 0.7 Hz, 3 H, CH ₃), 2.12–2.05 (m, 3 H), 1.90 (broad d, J = 2.8 Hz, 6 H), 1.82–1.71 (m, 6 H). ¹³C NMR (100 MHz, CDCl₃): δ = 148.48 (1C_q), 134.90 (1C_q), 128.81 (2CH), 124.72 (2CH), 43.30 (3CH₂), 36.87 (3CH₂), 35.85 (1C_q), 29.03 (3CH), 20.87 (1CH₃). 1-(4-Ethylphenyl)adamantane (3c): Mp 58 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.28 (half of an A₂X₂ system, 2 H), 7.15 (half of an A₂X₂ system coupled with CH₂, J _{with CH2} = 0.6 Hz, 2 H), 2.62 (q, J = 7.6 Hz, 2 H, CH ₂CH₃), 2.12–2.05 (m, 3 H), 1.91 (broad d, J = 2.8 Hz, 6 H), 1.82–1.71 (m, 6 H), 1.23 (t, J = 7.6 Hz, 3 H, CH₂CH ₃). ¹³C NMR (100 MHz, CDCl₃): δ = 148.68 (1C_q), 141.23 (1C_q), 127.55 (2CH), 124.75 (2CH), 43.29 (3CH₂), 36.87 (3CH₂), 35.88 (1C_q), 29.03 (3CH), 28.29 (1CH₂), 15.45 (1CH₃). 1-(4-Isopropylphenyl)adamantane (3d): Mp 87 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.28 (half of an A₂X₂ system, 2 H), 7.18 (half of an A₂X₂ system coupled with CH, J _{with CH} = 0.6 Hz, 2 H), 2.88 [qq, J = 6.9, 6.9 Hz, 1 H, CH(CH₃)₂], 2.12–2.05 (m, 3 H), 1.91 (broad d, J = 2.8 Hz, 6 H), 1.82–1.70 (m, 6 H), 1.24 [d, J = 6.9 Hz, 6 H, CH(CH ₃)₂]. ¹³C NMR (100 MHz, CDCl₃): δ = 148.74 (1C_q), 145.81 (1C_q), 126.09 (2CH), 124.69 (2CH), 43.29 (3CH₂), 36.88 (3CH₂), 35.87 (1C_q), 33.55 (1CH), 29.03 (3CH), 24.02 (2CH₃). 1-(4-Isobutylphenyl)adamantane (3e): Mp 34.5 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.25 (half of an A₂X₂ system, 2 H), 7.08 (half of an A₂X₂ system coupled with CH₂, J _{with CH2} = 0.6 Hz, 2 H), 2.44 (d, J = 7.2 Hz, 2 H, CH₂ of i-Bu), 2.12–2.05 (m, 3 H), 1.91 (broad d, J = 2.8 Hz, 6 H), 1.85 [tqq, J = 7.2, 6.6, 6.6 Hz, 1 H, CH(CH₃)₂], 1.82–1.70 (m, 6 H), 0.90 (d, J = 6.6 Hz, 6 H, CH(CH ₃)₂). ¹³C NMR (CDCl₃, 100 MHz): δ = 148.67 (1C_q), 138.70 (1C_q), 128.80 (2CH), 124.49 (2CH), 45.00 (CH₂), 43.30 (3CH₂), 36.89 (3CH₂), 35.88 (1C_q), 30.19 (1CH), 29.04 (3CH), 22.48 (2CH₃). Anal. Calcd for C₂₀H₂₈ (268.44): C, 89.49; H, 10.51. Found: C, 89.57; H, 10.46. 1-(4-tert-Butylphenyl)adamantane (3i): Mp 127.5 °C. ¹H NMR (CDCl₃, 400 MHz): δ = 7.34 (half of an A₂X₂ system, 2 H), 7.29 (half of an A₂X₂ system, 2 H), 2.12–2.05 (m, 3 H), 1.91 (d, J = 2.8 Hz, 6 H), 1.83–1.70 (m, 6 H), 1.31 [s, 9 H, C(CH ₃)₃]. ¹³C NMR (CDCl₃, 100 MHz): δ = 148.30 (1C_q), 148.06 (1C_q), 124.92 (2CH), 124.42 (2CH), 43.22 (3CH₂), 36.85 (3CH₂), 35.76 (1C_q), 34.25 (1C_q), 31.40 (3CH₃), 28.99 (3CH). 1,4-Di-1-adamantylbenzene (3j) ¹H NMR (400 MHz, CDCl₃): δ = 7.31 (s, 4 H), 2.12–2.05 (m, 6 H), 1.91 (d, J = 2.8 Hz, 12 H), 1.82–1.71 (m, 12 H). ¹³C NMR (100 MHz, CDCl₃): δ = 148.35 (2C_q), 124.45 (4CH), 43.21 (6CH₂), 36.86 (6CH₂), 35.79 (2C_q), 28.99 (6CH). For data of other compounds, see the Supporting Information.
• 23 For instance, no reaction was observed with 1 and isobutylbenzene at 40 °C in CCl₄. In 1,2-dichloroethane and 1-chlorobutane at 35–40 °C, the reactions of 1 with isobutylbenzene and tert-butylbenzene afforded complex mixtures.
• 24 Halobenzenes were not studied in CH₂Cl₂ as solvent because of their reduced reactivity and also due to the fact that InBr₃ was not a good catalyst in their case.
• 25 The same procedure as previously described was used, except that a reduced amount of aromatic substrate was used (see Table 3) and dichloromethane was added (its amount was adjusted by weight after flushing with nitrogen and stoppering).
• 26 Based on two experiments that were performed with toluene and ethylbenzene with HBr vented through a bubbler, no change was observed in reaction rate or selectivity (same para/meta ratios). Yields of 99% were obtained compared with 90 and 92% (InCl₃ as a catalyst).